Carcinoma of the pancreas is a highly lethal malignancy, the incidence of which is rising markedly. The current rate of cure is negligible, even with early diagnosis. for this reason, studies concerned with the etiology and pathogenesis of this devastating malignancy are clearly needed. An association between diabetes mellitus and pancreatic cancer has been recognized for over a century but the nature of this relationship is unknown. Two theories are proposed: first, that pre-existing diabetes mellitus predisposes to the development of pancreas cancer, and secondly, that diabetes mellitus results as a consequence of developing tumor within the pancreas. In the proposed study the relationship between diabetes and pancreas cancer will be examined by testing both of these hypotheses. Using a proven model of pancreatic cancer induced by N-nitrosobis(2-oxopropyl)amine (BOP), we will evaluate the question of whether diabetes predisposes to the development of pancreas cancer by examining: (1) whether alloxan, streptozotocin, or steroid diabetes potentiates the effects of known carcinogenic doses of BOP in the Syrian hamster, (2) whether diabetes potentiates the effects of subcarcinogenic doses of BOP in the Syrian hamster, (3) whether diabetes unmasks carcinogenesis of BOP in the Lewis rat, an animal ordinarily insensitive to BOP, and (4) whether spontaneous diabetes in the Chinese hamster increases sensitivity to BOP carcinogenesis. If diabetes can be shown to predispose to the development of pancreas cancer in these models, crossed pancreas transplants will be performed to determine if it is the diabetic pancreas or the diabetic state which leads to such predisposition. In the second section of the proposed study, the hopothesis that developing pancreas cancer causes diabetes will be examined by performing serial metabolic studies, serial determinations of pancreatic content of insulin, glucagon, and somatostatin, and serial quantitative studies of islet size, number, and cell population using immunohistologic techniques, at intervals during the development of pancreas cancer in the Syrian hamster. It is hoped in the course of these studies that the mechanism of the relationship between pancreatic cancer and diabetes will be elucidated, and that insight will be gained into the pathophysiology of both diseases.